Compounds containing a mercaptide group and method of producing same



Patented Apr. 28, 1936 UNITED STATES 2,038,609 COIHPOUNDS CONTAINlNG A MERCAPTIDE GROUP SAME Erwin Schwenk,

Berlin-Westend,

AND METHOD OF PRODUCING and Max Gehrke, Berlin-Halensee, Germany, assignors to Schering-Kahlbaum A. G., Berlin, Germany No Drawing. Application May 1, 1931, Serial No. 534,452. In Germany May 10, 1930 5 Claims.

Our invention relates to a new kind of organic compounds adapted for use as remedies and more especially to compounds containing a mercaptide group. It is an object of our invention to provide means whereby such compounds can be produced in a particularly favorable manner.

As is well known to those skilled in the art chemical compounds having a therapeutical value and containing heavy metals are produced frequently from organic compounds containing a reactive mercaptide group.

We have now found that the salts of compounds corresponding to the general formula Cn(H)n, wherein n is 2 or a higher integer, can

' be produced readilyrand with particularly good yield by causing'a compound of this kind comprising a reactive halogen atom to react with an alkali salt of a thio acid corresponding to the formula R-CO.SH wherein R is an aliphatic or aromatic radical and converting the thio ester thus produced into the mercaptide compound by saponification. The saponification can be carried through with the aid of an alcoholic ammonia solution or of alcohol and an alkali metal or an alcoholate.

This reaction occurs according to the general equations:

wherein a: is halogen, so that R110 is an organic halogen compound, such as for instance benzyl metal or ammonium, so that MSOCRz is the alkali salt of a thio acid, for instance of thio acetic acid or thiobenzoic acid or some other aliphatic or aromatic acids.

saponification according to Equation 2 can be carried through with the aid of an alcoholic ammonia solution or of alcohol and an alkali metal or an alcoholate. The saponification causes the production of the salt of the mercaptide compound.

Example 1 41 grs. aceto-bromo glucose and 11 grs. potassium thioacetate are dissolved under heating in '100 com. methanol. During the boiling of the solution potassium bromide will separate out after some time. After the reaction has come to an end the solution is allowed to cool down, ample quantities of white needles of pentaacetyl thioglucose separating out, which are freed from potassium bromide by washing with water. After recrystallization from methanol the compound has a melting point of 121 C., it is soluble in the usual organic solvents, dissolves only with difiiculty in benzene and is insoluble in water. By saponification with a solution of ammonia in methylalcohol according to the method described by Wrede in Zeitschrift fiir physiologische Chemie 119, p. 52, the'ammonium salt of thioglucose is obtained. 7

The reactionoccurs according to the following equations:

S-CO-OHs chloride, bromomethylsu-lfo acid, bromo-anthraquinon, aceto-bromo-glucose or aceto-bromo glycerine aldehyde, while M is an alkali-forming 2 aceto bromo glucose+potassium thioacetate: pentacetyl thioglucose+potassium bromide.

formed besides potassium thioacetate 13,2 grs. potassium xylothionate, forming white crystals s-oo-Grn S-NH4 HC H( 1 5 H--(\}'O'CO'CH3 H-Cl:-OHL (2) CHa-CO--( -H +6NH3+5H2O=HOCH +NH4O-OO-OH3 H-C-O-CO-CHa 0 H I 10 11-0 H-(J-ObO-OHa H 30H l H pentacetyl thioglucose ammonia ammonium melting at 160-165 C. and dissolving readily in 15 thioglucosate-kammonium acetate. water, less readily in alcohol, the compound being precipitated from its alcoholic solution by Example 2 ether or petrol ether. If 19 grs. gamma acetoxy alpha bromo alpha Example 4 beta propylene oxyde (described by H. O. L. Fisch- 20 er and Taube in Berichte der deutschen chemi- In a similar manner 34 grs. aceto-bromoschen Gesellschaft 60 p. 1705), 11 grs. potassium arabinose and 10 grs. sodium thioacetate will thioacetate and 300 com. methanol are treated as form 24,5 grs. tetraacetyl arabinothiose melting described with reference to Example 1, there is at 78 C. By saponification with sodium methobtained gamma acetoxy alpha acetyl thio alpha ylate (obtained by dissolving 1,38 grs. sodium 5 beta propylene oxyde forming white needles in '75 com. methyl alcohol) this compound is demelting at 160 C. and being soluble in pyridine composed into sodium thioacetate and sodium and benzene, less readily soluble in methanol arab-inothiosate (12,3 grs.). The sodium araband insoluble in benzene and water. By saponiinothiosate forms white crystals which dissolve fi at Of this compound 8 Salt (Corresponding readily in water, less readily in alcohol and can to the saponifyine agent used) of the mm be precipitated from their alcoholic solution by oxy alpha thio alpha beta propylene oxyde is ether or petrol ether. obtained. These salts are colorless compounds Ema mp1 8 5 dissolving readily in water, less readily in alcohol and being precipitated in crystalline form In a similar manner reaction between gamma 35 from their alcoholic solutions by ether or petrol acetoxy alpha bromo alpha beta propylene oxyde ether. With the salts of heavy metals the heavy and Potassium thioacetate W ll re t in the metal salts of gamma oxy alpha thio alpha beta formation of gamma oxy alpha thio alpha beta propylene oxyde are formed. by double converpropylene oxyde diacetate melting at 158 C., sion. The reaction occurs according to the folthis compound being decomposable into sodium 40 lowing equations: gamma oxy alpha thio alpha beta propylene s-oo-oHl Br I +K-SO O-GH5= +K Br HC-O-CO-CH3 l H-o-O-oo-om H l H gamma acetoxy alpha bromo alpha beta propylene oxyde and acetate by saponification with potasoxyde-l-potassium thioacetate==gamma acetoxy sium alcoholate. alpha acetylthio alpha beta propylene oxyde+po- Various changes may be made in the details tassium bromide disclosed in the foregoing specification without SNa s-o 0-011: l HO\ H0 H--O I +3NaOH= H-OO- 0 0-011; +2 NaO-C O'CHs-l-EhO l HO-OH H l H 5 Example 3 6 If 34 grs. aceto-bromo-xylose are boiled during 5 minutes with a solution of 12 grsfp'otassium acetate in150 ccm. ethyl alcohol, the mixture being treated as described with reference to Example 1, there result 22,6 grs. tetraacetylxylose melting at 99 C. By saponifying this compound with potassium ethylate, which has been obtained by dissolving 2,57 grs. potassium in 100 com. absolute ethyl alcohol, there is departing from the invention or sacrificing the V advantages thereof.

We claim:

1. The method of producing an alkali metal mercaptide compound of a carbohydrate of the general formula Cn(H20)n, wherein n represents 3, 4, 5 or 6, which comprises reacting an acetohalogen compound of said carbohydrate with the salt of athio acid and decomposing the ester thus obtained by saponification' with a wherein X is halogen, to react with the salt of a thio acid and decomposing the ester thus obtained by saponification with a saponifying alkali metal compound to form a thiosate and a salt of the acid.

3. The method of producing an alkali metal glucothiosate comprising acting on aceto-bromoglucose with alkali metal thioacetate and decomposing the pentacetyl thioglucose which has formed in the reaction into alkali metal thioglucosate and alkali metal acetate by saponification with a saponifying alkali metal compound.

4. The method of producing an alkali metal salt of gamma oxy alpha thio alpha beta propylene oxyde comprising causing reaction between gamma acetoxy alpha bromo alpha beta propylene oxyde and alkali metal thioacetate and decomposing the gamma acetoxy alpha acetyl thio alpha beta propylene oxyde formed in the reaction by saponification with a saponifying alkali metal compound.

5. As a new product an alkali metal salt of gamma oxy alpha thio alpha beta propylene oxide being colorless, dissolving readily in water, less readily in alcohol and being precipitated in the form of crystals from its alcoholic solution by ether or petrol ether.

ERWIN SCHWENK. MAX GEHRKE. 

